Over the past two years, the development of optical tomography using near-infrared excitable fluorescent contrast agents has progressed in a few laboratories using re-emitted fluorescence measurements at single point positions surrounding the phantom or animal in response to incident point illumination of excitation. Limitations in the volume of tissue interrogated point illumination and the clinically unrealistic scanning or circumferential measurements around the entire boundary of the tissue to be imaged are problematic for clinical translation. In contrast, ALL studies of NIR fluorescent contrast agent dye developments have been evaluated with incident plane wave excitation and area detection of re-emitted fluorescence, - an approach that enables illumination of greater tissue volumes and more rapid measurements on a single surface. Yet tomographic algorithms have focused only point illumination and point measurements surrounding the boundaries. In this application, we propose to develop a unique and novel tomographic algorithm employing a CONstrained Truncated Newton approach, or CONTN, developed by the P.I. for fluorescence enhanced optical tomography. This work seeks to demonstrate tomographic reconstructions using CONTN from plane wave excitation and area collection of fluorescence in reflectance geometry in order to reconstruct the 3'D target position as well as agent concentration and fluorescence decay parameters. This high dsk application seeks to evaluate CONTN as a function target depth, fluorescence lifetime and absorption contrast, and target size and number. The milestone of this R21 application will be the demonstration of a unique and novel 3-D tomographic reconstruction approach from reflectance measurements made on the surface of tissue phantoms. If successful this work will demonstrate that x-y surface fluorescence measurements can be used to ascribe x-y-z images for assessing target depth and size enabling further development of a hand-held, NIR fluorescence imaging system for imaging as deep as 3-4 centimeters. The overall goal of this R21 application is to develop the approach and algorithms demonstrating the feasibility for a hand-held optical imaging device, akin to ultrasound, which would provide rapid image information for the localization of target tissues.